Detection Of Gene Mutations In Two Families With Epidermolytic PalmoPlantar Keratoderma And One Family With Erythrokeratodermia Variabilis

Background:EPPK is an autosomal dominant genetic disease,mainly caused by KRT9 gene mutation,and EKV is also an autosomal dominant genetic disease.It is mainly caused by GJB3 and GJB4 gene mutations.Objective:Detect the mutations of KRT1 gene and KRT9 gene in families with EPPK and the mutations of GJB3 and GJB4 genes in families with EKV.Methods:All clinical data of patients with 2 EPPK families and 1 EKV family in our hospital were collected.The exons of KRT1、KRT9、GJB3 and GJB4 gene were amplified by polymerase chain reaction and sequenced by Sanger sequence from peripheral blood of 10 family patients,5 normal subjects and 200 healthy volunteers.All gene mutations were sorted out and analyzed in combination with clinical manifestations.Results:the missense mutation c.487C>T was detected in exon 1 of KRT9 gene in all patients in two families of EPPK,which had previously been reported as a hot spot mutation.In one of the families,the daughter of the proband developed congenital finger flexion in addition to hyperkeratosis of the palmoplantar,and the grandfather of the proband also developed congenital knuckle pad in addition to hyperkeratosis of the palmoplantar,The symptom was not found in other patients in the family and in the second family.A novel mutation c.148G>T was detected in exon 1 of GJB3 gene in all patients in EKV family.The skin damage of the proband’s mother is more serious than that of the proband.Conclusion:The c.487C>T missense mutation of KRT9 gene is the genetic cause in these two EPPK families.The novel c.148g>T missense mutation of GJB3 gene is the genetic cause of the EKV family.The phenotypes of the same mutation were different in different families or different individuals in the same family.